Table Of ContentCancer Chemotherapy 1
7
Cancer Treatment and Research
WILLIAM L. MCGUIRE, series editor
I. R.B. Livingston, ed., Lung Cancer I. 1981. ISBN 90-247-2394-9.
2. G. B. Humphrey, L. P. Dehner, G. B. Grindey and R. T. Acton, eds., Pediatric Oncology I.
1981. ISBN 90-247-2408-2.
3. J.J. DeCosse and P. Sherlock, eds., Gastrointestinal Cancer I. 1981. ISBN 90-247-2461-9.
4. lM. Bennett, ed., Lymphomas I, including Hodgkin's Disease. 1981. ISBN 90-247-2479-1.
5. C. D. Bloomfield, ed., Adult Leukemias I. 1982. ISBN 90-247-2478-3.
6. D. F. Paulson, ed., Genitourinary Cancer I. 1982. ISBN 90-247-2480-5.
Cancer Chemotherapy 1
edited by
F. M. MUGGIA
New York University Medical Center
I I
1983
MARTINUS NUHOFF PUBLISHERS
THE HAGUE / BOSTON / LONDON
Distributors:
for the United States and Canada
K1uwer Boston, Inc.
190 Old Derby Street
Hingham, MA 02043
USA
for all other countries
K1uwer Academic Publishers Group
Distribution Center
P.O. Box 322
3300 AH Dordrecht
The Netherlands
Library of Congress Cataloging in Publication Data
Cancer chemotherapy 1.
(Cancer treatment and research ; v. 7)
Includes index.
1. Cancer--Chemotherapy. 2. Antineoplastics
agents. I. Muggia, Franco M. II. Series.
[DNLM: 1. Antineoplastic agents--Period.
2. Neoplasms--Drug therapy--Period. WI CA693
v. 7 etc.]
RC271.C5C313 1982 616.99'4OCl 82-8229
ISBN·13: 978·1·4613·3905·2 e·ISBN·13: 978·1·4613·3903·8
001: 10.1007/978·1·4613·3903·8
Copyright © 1983 by Martinus Nijhoff Publishers. The Hague.
All rights reserved. No part of this publication may be reproduced. stored in a retrieval system. or
transmitted in any form or by any means. mechanical. photocopying. recording. or otherwise.
without the prior written permission of the publisher.
Martinus Nijhoff Publishers. P.D. Box 566. 2501 CN The Hague. The Netherlands.
Contents
Foreword VII
Preface IX
List of contributors xiii
1. Relevance of drug resistance in cancer treatment strategy
J.H. GOLDIE
2. Animal models for drug scheduling 31
L. M. VAN PUTTEN and M. B. EDELSTEIN
3. Animal models for cancer chemotherapy 65
A. GOLDIN
4. The human tumor cloning assay: An in vitro assay for antitumor
activity in solid tumors ................. 103
1. D. COWAN and D. D. VON HOFF
5. The anthracycline antibiotics: New directions in drug develop-
ment and cancer treatment . . . . . . . . . . . . . . . . 123
F. M. MUGGIA and M. ROZENCWEIG
6. Cisplatin in cancer therapy: Optimization of treatment regimens
and toxicity protection . . . . . . . . . . . . . . . . . . 149
1. S. PENTA, F. M. MUGGIA and P. A. SALEM
7. Platinum analogues: Criteria for selection 171
K.R. HARRAP
8. Chemotherapy based on amino acid depletion and amino acid
antagonists . . . . . . . . . . . . . . . . . . . .. 219
w. KREIS
9. Chemotherapy of testicular cancer: From palliation to cure 249
F. CAVALLI
10. The impact of chemotherapy on the treatment of gastric cancer 281
D.L. KISNER and J.S. MACDONALD
11. Therapy of acute myelogenous leukemia 303
K. A. FOON and R. P. GALE
Index 333
Cancer Treatment and Research
Foreword
Where do you begin to look for a recent, authoritative article on the
diagnosis or management ofa particular malignancy? The few general onco
logy textbooks are generally out of date. Single papers in specialized journals
are informative but seldom comprehensive; these are more often prelimi
nary reports on a very limited number of patients. Certain general journals
frequently publish good indepth reviews of cancer topics, and published
symposium lectures are often the best overviews available. Unfortunately,
these reviews and supplements appear sporadically, and the reader can nev
er be sure when a topic of special interest will be covered.
Cancer Treatment and Research is a series of authoritative volumes
which aim to meet this need. It is an attempt to establish a critical mass of
oncology literature covering virtually all oncology topics, revised frequently
to keep the coverage up to date, easily available on a single library shelf or
by a single personal subscription.
We have approached the problem in the following fashion. First, by div
iding the oncology literature into specific subdivisions such as lung cancer,
genitourinary cancer, pediatric oncology, etc. Second, by asking eminent
authorities in each of these areas to edit a volume on the specific topic on an
annual or biannual basis. Each topic and tumor type is covered in a volume
appearing frequently and predictably, discussing current diagnosis, staging,
markers, all forms of treatment modalities, basic biology, and more.
In Cancer Treatment and Research, we have an outstanding group of
editors, each having made a major commitment to bring to this new series
the very best literature in his or her field. Martinus Nijhoff Publishers has
made an equally major commitment to the rapid publication of high quality
books, and world-wide distribution.
Where can you go to find quickly a recent authoritative article on any
major oncology problem? We hope that Cancer Treatment and Research
provides an answer.
WILLIAM L. MCGUIRE
Series Editor
Preface
The field of cancer chemotherapy is completing its fourth decade of
existence. Parallels between progress in treatment of infectious disease and
cancer are becoming more apparent than at the outset. The slowness in
developing effective cancer chemotherapy has met with the same degree of
skepticism found during the pre-penicillin era. Many disappointments have
emerged in common: the recognition of resistant types, the emergence of
resistance in spite of initial susceptibility, the appearance of unexpected
toxic manifestations of new treatment modalities, the heterogeneity of the
population that must be destroyed, and many others. Such skepticism has
led some to totally reject the pursuit of research into new chemotherapeutic
drugs as a fruitless endeavor. In addition, there has been continuous resur
gence of interest into other therapeutic approaches and host factors which
might control malignant growth. While such efforts might bear fruits of
considerable importance they are also reminiscent of the interest in host
immunity in the treatment oftuberculosis, prior to the development of very
effective chemotherapy. Moreover, the denunciation of lack of progress
overlooks the abundant activity which is taking place and which is steadily
improving the treatment of many types of neoplasia. This volume, the first
of a series, will collect in a concentrated form the various ingredients of
chemotherapeutic progress. Totally new areas under development will also
be presented, although it may be several years before success in the clinic
from such approaches will be established.
Progress in a field may be heralded by conceptual advances and by intro
duction of new technologies. Accordingly the book begins with a focus on
the importance of drug resistance. Goldie develops through mathematical
models and concrete examples the foundations of a strategy of early effec
tive therapy, alternating non-cross resistant chemotherapy and combined
modality treatment. His concepts restate in a clear fashion previously hailed
theories or experimental results. Van Putten and Edelstein go beyond the
x
mathematical modeling to various aspects that affect the outcome of treat
ment once it is applied, and to the variables which are implicit in rational
scheduling (including cell kinetic, pharmacokinetic, biochemical and other
aspects). Having dissected the complexity of factors determining treatment
outcome we are updated on the use of animal tumor models by Goldin.
These studies have played a major role in screening for anticancer drugs and
in developing therapeutic strategies. However, appreciation for the short
comings of animal tumors coupled with availability of human tumor xeno
grafts have led to a reassessment of such models in developing cancer chem
otherapy. A new dimension has been added both in screening and in devel
oping therapeutics strategies by the introduction of in vitro human tumor
cloning assays. Progress in this burgeoning field is comprehensively covered
by Cowan and Von Hoff.
Technological advances may not enable one to encounter new paths of
knowledge, but are extremely helpful in consolidating areas which appear
promising. To follow' one's nose' is an important aspect of human discov
ery and has been utilized in the search for improvement in therapeutic
index of anticancer drugs. The study of anthracycline antibiotics represents
an example of the comprehensiveness of such a search: from dose schedule
alterations and protection of specific toxicity to analogue development
based on animal tumor studies. While the success of these approaches sum
marized by Muggia and Rozencweig will not be known for some time, this
quest is being progressively illuminated by a better appreciation of anthra
cycline antitumor effect and toxic manifestations. Similarly second genera
tion platinum compounds have not yet replaced cisplatin in any clinical
circumstance. However, the delineation of cisplatin nephrotoxicity by Penta
et al., coupled with the exhaustive search for analogues summarized by
Harrap, augurs well for optimization of the clinical utility of these antitu
mor drugs. I have also selected a relatively unexploited area in cancer che
motherapy, the depletion or antagonism of amino acids, reviewed by Kreis.
This presentation should serve to stimulate interest into a new target to be
exploited in our efforts to achieve selective destruction of cancer cells.
The successful application of cancer chemotherapy has usually required a
multipronged attack consisting of drug combinations and combined modal
ities. Thus the identification of new targets for selective action of anticancer
drugs continues to hold promise of future therapeutic progress. This prom
ise has been vastly fulfilled in the treatment of testicular cancer as described
by Cavalli, and has just become perceptible in gastric cancer as described by
Kisner and MacDonald. Finally, improved knowledge of tumor biology,
diagnostic and therapeutic concepts can lead to an intellectually satisfying
progressive assault on a disease. This is best exemplified by the strategies
employed in acute leukemia as described by Foon and Gale. Testicular can-
XI
cer represents yet another demonstration of how therapeutic advances can
be effectively implemented through use of tumor markers and diagnostic
innovations.
Thus begins a concentrated look at cancer chemotherapy in 1982. Al
though not meant to be comprehensive, the objective of the series is to
upgrade concepts in therapeutic strategy, update preclinical studies, review
development in the major classes of compounds, identify new directions,
and provide some landmarks of current clinical progress. The reader hope
fully will have grasped the foundations of current therapies, and gained a
perspective of future developments.
F. M. Muggia,
New York
List of Contributors
CAVALLI, F., Servizio Oncologico, Ospedale San Giovanni, 6500 Bellinzona,
Switzerland.
COWAN, 1. D., Oncology Service, Brooke Army Medical Center, Fort Sam
Houston, TX 78234, U.S.A
EDELSTEIN, M. B., Radiobiological Institute TNO, Lange Kleiweg 151, P.O.
Box 5815, 2280 HV Rijswijk, The Netherlands.
FOON, K. A, Biological Research and Therapy Branch, Biological Response
Modifiers Program, Division of Cancer Treatment, National Cancer In
stitute, Frederick Cancer Research Facility, Frederick, MD 21701,
U.S.A
GALE, R. P., University of California School of Medicine, Los Angeles, CA
90024, U.S.A
GOLDIE, 1. H., Cancer Control Agency of British Columbia, 2656 Heather
Street, Vancouver, B.c. V5Z 3J3, Canada.
GOLDIN, A, Division of Cancer Treatment, National Cancer Institute,
Bethesda, MD 20014 and Division of Medical Oncology, Vincent T.
Lombardi Cancer Research Center, Georgetown University School of
Medicine, Washington, D.C. 20007, U.S.A
HARRAP, K. R., Department of Biochemical Pharmacology, Institute of
Cancer Research, Royal Marsden Hospital, Block E, Clifton Avenue, Bel
mont, Sutton, Surrey SM2 5PX, England.
KISNER, D. L., Department of Medicine, Division of Oncology, University
of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive,
San Antonio, TX 78284, U.S.A.
KREIS, W., Memorial Sloan-Kettering Cancer Center, New York, NY 10021,
U.S.A Present address: North Shore University Hospital, 300 Commun
ity Drive, Manhasset, NY 11030, U.S.A
MACDONALD, 1. S., Cancer Therapy Evaluation Program, Division of Can
cer Treatment, National Cancer Institute, Bethesda, MD 20205, U.S.A
